Sodium tetramethoxyborate: an efficient catalyst for Michael additions of stabilized carbon nucleophiles

Sodium tetramethoxyborate, easily prepared by reaction of inexpensive sodium borohydride with methanol, possesses a suitable combination of a Lewis base and a Lewis acid to catalyze Michael reactions at room temperature under practically neutral conditions. This reaction provides good to excellent yields of Michael addition products from a broad scope of Michael donor and Michael acceptor reagents.     

Synthesis of 9-substituted 1,8-dioxooctahydroxanthenes by using diethyl ethoxymethylenemalonate as a double Michael acceptor synthon

Tandem Michael addition/elimination/Michael addition/cyclization reactions of diethyl ethoxymethylenemalonate as a double Michael acceptor with cyclic ??-diketones furnished novel 9-substituted 1,8-dioxooctahydroxanthenes.     

Ruthenium-catalyzed decarboxylative insertion of electrophiles

[reaction: see text]. A ruthenium complex, Cp*Ru(bipyridyl)Cl, has been developed as a catalyst for the first regioselective tandem Michael addition-allylic alkylation of activated Michael acceptors. The net transformation is the decarboxylative insertion of Michael acceptors into allyl beta-ketoesters.     

迈克尔反应受体分子化学生物学研究

迈克尔受体是烯键或炔键与吸电子基团共轭相连形成的官能团,含有这样官能团的化学小分子能与亲核试剂发生迈克尔加成反应,因此称为迈克尔反应受体分子。迈克尔反应受体分子是一类重要的生理活性分子,它们直接或间接参与许多生命过程,同时也是细胞中许多信号转导途径的调节者,在化学生物学研究中起着重要的作用。本文对迈克尔反应受体分子化学生物学研究进展进行了综述。     

Enantioselective organocatalytic Michael additions of aldehydes to enones with imidazolidinones: cocatalyst effects and evidence for an enamine intermediate

An enantioselective intermolecular Michael addition of aldehydes to enones catalyzed by imidazolidinones has been achieved. Chemoselectivity (Michael addition vs aldol) can be controlled through judicious choice of hydrogen-bond-donating cocatalysts. The optimal imidazolidinone/hydrogen-bond-donor pair affords Michael addition products in excess of 90% ee. Furthermore, we have isolated and characterized an enamine intermediate and demonstrated its efficacy as a nucleophile in the observed Michael addition reactions.     

Highly stereoselective Michael reduction/intramolecular Michael reaction cascade to synthesize trans-stereodiad comprising an all-carbon quaternary stereogenic center

A highly stereoselective Michael reduction/intramolecular Michael reaction cascade is described. The cascade is initiated by the regioselective Michael reduction of an α-methylidene ester with L-Selectride. This is followed by the highly stereoselective intramolecular Michael reaction which efficiently constructs a six-membered carbocyclic ring with formation of the trans-stereodiad, composed of an all-carbon quaternary center and a tertiary stereogenic center. The stereoselectivity is perfectly controlled by the choice of alkene geometry in the Michael acceptor.     

Tandem Michael addition of amines to maleic anhydride and 1,3-prototropic shift: experimental and theoretical results

Amines, namely diethylamine, diphenylamine, benzylamine, and pyrrolidine react with maleic anhydride to form Michael adducts. The Michael adducts formed with the first three amines undergo tandem 1,3-prototropic shift to give the final products. Computational calculations at the DFT (B3LYP/6-31+G*) level reveal that a reactant-complex formed between the initially formed Michael adduct and the respective amine plays a crucial role in the 1,3-prototropic shift. In the reaction of pyrrolidine with maleic anhydride, Michael addition is not followed by 1,3-prototropic shift. The theoretical studies of the latter reaction show that a reactant-complex is not formed in this case. Dimethyl maleate and dimethyl fumarate react with pyrrolidine to give the same Michael addition product.     

Switchable Stereocontrolled Divergent Synthesis Induced by aza‐Michael Addition of Deactivated Primary Amines under Acid Catalysis

Switchable tandem intramolecular aza‐Michael/Michael and double aza‐Michael reactions allow the oriented synthesis of highly functionalised cyclic skeletons. Conjugate addition of deactivated anilines triggers chemo‐ and stereo‐divergent ring‐closure reaction pathways with a striking selectivity depending on reaction conditions.     

N-heterocyclic carbene catalyzed umpolung of Michael acceptors for intermolecular reactions

leahciM! The N-heterocyclic carbene catalyzed umpolung of Michael acceptors proceeds through the formation of a deoxy-Breslow intermediate (see scheme; EWG=electron-withdrawing group). This nucleophilic species can react with other Michael acceptors in an intermolecular fashion, thereby resulting in the formation of homo- or heterodimeric olefins. This "Michael umpolung" should become a valuable method for the formation of densely functionalized olefins.     

In Situ Observation of Thiol Michael Addition to a Reversible Covalent Drug in a Crystalline Sponge

A reversible Michael addition reaction between thiol nucleophiles and cyanoenones has been previously postulated to be the mechanism‐of‐action of a new family of reversible covalent drugs. However, the hypothetical Michael adducts in this mechanism have only been detected by spectroscopic methods in solution. Herein, the crystallographic observation of reversible Michael addition with a potent cyanoenone drug candidate by means of the crystalline‐sponge method is reported. After inclusion of the cyanoenone substrate, the sponge crystal was treated with a thiol solution. Subsequent crystallographic analysis confirmed the single‐crystal‐to‐single‐crystal transformation of the substrate into the impermanent Michael adduct.     

Synthesis of isoxazolobenzoxepanes via Michael addition of indoles to nitroalkenes and sequential intramolecular nitrile oxide cycloaddition

Nitroalkenes derived from O-propargyl salicylaldehyde undergo facile Michael addition with indoles leading to indole-derived Michael adducts. Intramolecular nitrile oxide cycloaddition (INOC) of the Michael adducts results in isoxazolobenzoxepanes in good to excellent yields.     

Use of odorless thiols: formal asymmetric Michael addition of hydrogen sulfide to alpha-substituted alpha,beta-unsaturated carbonyl compounds

[reaction: see text] The Michael addition to alpha-substituted alpha,beta-unsaturated esters and amides using complex A containing a chiral odorless thiol proceeded diastereoselectively. The Michael adducts were converted to beta-mercapto esters and amides via a Wagner-Meerwein rearrangement with boron trifluoride etherate and a thiol exchange reaction using odorless 1-dodecanethiol. This conversion constitutes a formal asymmetric Michael addition of hydrogen sulfide to alpha,beta-unsaturated carbonyl compounds using odorless thiols instead of the toxic hydrogen sulfide.     

Amine-catalyzed Michael reactions of an aminoaldehyde derivative to nitroolefins

Catalytic enantioselective Michael addition reactions of α-amino functionalized aldehydes to nitroolefins have been developed. The Michael product was obtained in up to 98% ee, but the enantiomeric purity of the Michael product was decreased during isolation of the product.     

Antibody-catalyzed asymmetric intramolecular Michael addition of aldehydes and ketones to yield the disfavored cis-product

The development of new catalytic asymmetric reactions continues to be a major goal in organic chemistry. Here we report a novel antibody-catalyzed intramolecular Michael addition of aldehydes and ketones to enones. The reaction is enantioselective and diastereoselective with a high ee value and cis/trans ratio. This is the first example of asymmetric intramolecular Michael addition of ketones. Antibody 38C2 is the only catalyst to date capable of generating this selectivity in Michael addition products.     

Michael Reaction of 2,4-Dioxohexahydro-1,3,5-triazine

With the extensive investigation of the Michael reaction, not the methylene compounds activated by electron withdrawing group[1,2] but other activated unsaturated compounds containing such as activate N-H or O-H have been used as Michael acceptor.[3,4] However, the research on the Michael reaction of 2,4-dioxohexahydro-1,3,5-triazine (DHT) has not been reported. After the systematic researches on the substitution reactions of DHT, we first report the Michael reaction of DHT with acrylic esters in this paper.     

Selective Michael Reaction Controlled by Supersilyl Protecting Group

Selective Michael reaction of organolithium reagents to supersilyl methacrylate is reported. The method was able to control a single and double Michael addition. The successful termination of the process using the supersilyl protecting group allows for the controlled, chemoselective, and diastereoselective Michael reaction.     

Template effects of vesicles in dynamic covalent chemistry

Vesicle lipid bilayers have been employed as templates to modulate the product distribution in a dynamic covalent library of Michael adducts formed by mixing a Michael acceptor with thiols. In methanol solution, all possible Michael adducts were obtained in similar amounts. Addition of vesicles to the dynamic covalent library led to the formation of a single major product. The equilibrium constants for formation of the Michael adducts are similar for all of the thiols used in this experiment, and the effect of the vesicles on the composition of the library is attributed to the differential partitioning of the library members between the lipid bilayer and the aqueous solution. The results provide a quantitative approach for exploiting dynamic covalent chemistry within lipid bilayers.

Vesicle lipid bilayers have been employed as templates to modulate the product distribution in a dynamic covalent library of Michael adducts formed by mixing a Michael acceptor with thiols.     

Synthesis of nitro-substituted decalones by double Michael reaction,sequential Michael reaction,and by Diels-Alder reaction

4-Nitro-3-phenyl-decalones are obtained from 1-acetylcyclohexene by three different ways. Stereochemistry and reaction pathways are discussed, and, for the first time, an intermediate of a sequential Michael reaction is isolated.The Michael reaction is of great preparative value for the formation of CC bonds². We are especially interested in the stereochemistry of the double Michael reaction     

Enantioselective Michael Addition of Water

The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β‐hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti‐stereochemistry.     

Diversity-oriented synthesis of polycyclic diazinic scaffolds

An efficient and versatile synthesis of a polycyclic diazinic system starting from oxazine has been developed using a two-step Michael/retro Michael and cyclization sequence. The substrates were synthesized with good to high yields giving rapid access to molecular diversity.